MUC5B

protein-coding

mucin 5B, oligomeric mucus/gel-forming, the group of Mucins|MicroRNA protein coding host genes

Gene summary

This gene encodes a member of the mucin family of proteins, which are highly glycosylated macromolecular components of mucus secretions. This family member is the major gel-forming mucin in mucus. It is a major contributor to the lubricating and viscoelastic properties of whole saliva, normal lung mucus and cervical mucus. This gene has been found to be up-regulated in some human diseases, including sinus mucosa of chronic rhinosinusitis (CRS), CRS with nasal polyposis, chronic obstructive pulmonary disease (COPD) and H. pylori-associated gastric disease, and it may be involved in the pathogenesis of these diseases. [provided by RefSeq, Jul 2010]

Previous symbols:

MUC5

MANE transcript

NM_002458.3

Inheritance

AR, AD

ClinVar variants

P:2U:1359B:445

Top phenotype

Interstitial lung disease 2

gnomAD constraint

pLI —, LoF o/e 0.18

Max pathogenic AF

—

Genomic locus

chr11:1,223,066-1,262,172

External References & Databases

Ensembl (ENSG00000117983)

Transcript & Mutation Effects

hg38 • Region Span ~39.1 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

interstitial lung diseaseLIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0015925

Submitter: Ambry Genetics

interstitial lung disease 2LIMITED

Inheritance Pattern: AD

Disease ID:MONDO:0800497

Submitter: PanelApp Australia

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to MUC5B variants in ClinVar

6 Conditions Cataloged

not specifiedTotal: 1517

not providedTotal: 372

Interstitial lung disease 2Total: 23

MUC5B-related disorderTotal: 12

Susceptibility to severe COVID-19Total: 1

Pulmonary fibrosisTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_002458.3. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			9 clinvar	169 clinvar	20 clinvar	198
missense			1338 clinvar	233 clinvar	23 clinvar	1594
nonsense		1 clinvar	3 clinvar			4
start loss						0
frameshift		1 clinvar	4 clinvar			5
splice donor/acceptor (+/-2bp)			5 clinvar			5
Total	0	2	1359	402	43	1806

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 3 of 3 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_002458.3	RefSeq	NP_002449.2	49	MANE Select
ENST00000529681.5	Ensembl	ENSP00000436812.1	49	MANE Select
ENST00000526859.1	Ensembl	ENSP00000434539.1	6	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Salivary secretion - Homo sapiens (human)
IL-17 signaling pathway - Homo sapiens (human)
Lung fibrosis
Post-translational protein modification
Dectin-2 family

Biological Process

stimulatory C-type lectin receptor signaling pathway
O-glycan processing

Molecular Function

protein binding

Cellular Component

extracellular space
Golgi lumen
plasma membrane
intracellular membrane-bounded organelle
extracellular exosome

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000529681
Coding exons: 49
Length: 39111
Individuals with no LoFs: 124724
Homozygous LoFs: 0
Heterozygous LoFs: 63
Defined: 124787
p: 0.000252

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-2.84	3816	3.35e+3	1.14	0.000221	36101
Missense (PolyPhen)		85	69.407	1.2247		672
Synonymous	-10.4	2073	1.55e+3	1.34	0.000119	13090
Loss of Function	9.68	30	164	0.183	0.00000784	1792

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00046	0.00045	rare
Latino/Admixed American	0.00015	0.00014	rare
Ashkenazi Jewish	0.00041	0.00040	rare
East Asian	0.00023	0.00022	rare
Finnish	0.00014	0.00014	rare
European (Non-Finnish)	0.00035	0.00032	rare
South Asian	0.00011	0.000098	rare
Other	0.00033	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Gel-forming mucin that is thought to contribute to the lubricating and viscoelastic properties of whole saliva and cervical mucus.;
Disease: DISEASE: Pulmonary fibrosis, idiopathic (IPF) [MIM:178500]: A lung disease characterized by shortness of breath, radiographically evident diffuse pulmonary infiltrates, and varying degrees of inflammation and fibrosis on biopsy. In some cases, the disorder can be rapidly progressive and characterized by sequential acute lung injury with subsequent scarring and end-stage lung disease. {ECO:0000269|PubMed:21506741, ECO:0000269|PubMed:21506748}. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry. A common polymorphism in the promoter of MUC5B is associated with familial interstitial pneumonia and idiopathic pulmonary fibrosis, suggesting that dysregulated MUC5B expression in the lung may be involved in the pathogenesis of pulmonary fibrosis (PubMed:21506741). {ECO:0000269|PubMed:21506741}.;

Intolerance Scores

LoFtool: 0.243
RVIS EVS: 16.52
RVIS percentile EVS: 99.98

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Indispensability pred.: E
Indispensability score: 0.612

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	High	High	High
Primary Immunodeficiency	High	High	High
Cancer	High	High	High